A new study discovered that the endocannabinoidome (also written eCBome) is directly controlled by gut microbes. This new study is very important because the endocannabinoid system actually interacts with the gut microbiota on a number of metabolic pathways to influence numerous areas of health. These include obesity, atherosclerosis, pain, memory, sleep, appetite or visceral hypersensitivity.

What is the endocannabinoidome?

This term has been introduced by one of the most important researchers in this field, the Prof. Vincenzo Di Marzo. He has defined the endocannabinoidome as a very complex system composed of more than hundreds of different fatty acid-derived mediators and more than fifty different receptors and enzymes catalysing the synthesis or the degradation of these lipids.

Why investigating the endocannabinoid system?

This complex system is becoming more and more popular, thanks to the impact of the molecules it produced on the regulation of many physiological systems ranging from the regulation of appetite, energy storage in fat, energy expenditure, but also the regulation of inflammation, immunity, pain, and even behaviour  such as stress, anxiety, or even addiction!

Therefore, this system is very attractive not because of its name and potential reference to cannabis! The endocannabinoid system and the endocannabinoidome mediators are bioactive lipids ultimately derived from long-chain fatty acids also binding to receptors similar to the ones initially discovered as responsible for the effects of the active compound of cannabis (THC) (the cannabinoid receptors 1 and 2, CB1 and CB2).

Nowadays, it is commonly admitted that our diet and the sources of fatty acids really matter for this endocannabinoidome! But not only… GUT MICROBES are playing a major role.

Gut Bacteria interact with Endocannabinoids

The idea that gut microbes dialogue with the endocannabinoid system has been one of my motivations since 2005. And in 2010, together with my team and Prof. Giulio Muccioli, we published the discovery that the endocannabinoid system is strongly regulated by the gut microbiota. Indeed, playing with the microbiota using prebiotics, probiotics or antibiotics and even in  germ-free mice (i.e. mice without microbiota) was always linked with a change in the expression of the canonical members of this endocannabinoid system.

This led us to discover that the gut microbiota was also controlling the gut barrier function by a mechanism linked with the main receptor CB1, but also that the expansion of the adipose tissue observed during obesity could also be associated with the regulation of the endocannabinoid system.  Our finding that CB1 regulation of gut barrier was under the control of the gut microbiota is probably another mechanism by which CB1 regulates the onset of inflammation in addition to direct pro-inflammatory effects. Therefore… any activation of CB1 receptors in the gut can also lead to gut permeability!

The gut microbiota was also controlling the gut barrier function!

What is really new with this study?

This new study is very important because this is not a confirmation of previous findings! This study is the first study going very deep into the analysis of the endocannabinoidome. They have analysed the impact of microbial transplantation on the eCBome throughout the gastrointestinal tract with more than 50 genes and more than 20 different lipids from the endocannabinoidome. That is a very profound and thorough analysis of this system.

And the overall results are clearly showing that many molecules from the endocannabinoidome are tightly regulated by the gut microbiota.

Is this useful for therapeutic applications?

It is too early to translate these data into human applications or potential therapy, but they have clearly the merit to pave the way for further investigations. This also strongly suggests that we have (once again) to take into account the gut microbes and their impact on the regulation of genes involved in the response to some drugs or to some nutrients and eventually on health.

Source: Manca C. et al., JLR, First Published on November 5, 2019.